Opinion
VIEWPOINT
Hossein Alinia, MD Center for Dermatology Research, Department of Dermatology, Wake Forest School of Medicine, WinstonSalem, North Carolina. Steven R. Feldman, MD, PhD Center for Dermatology Research, Department of Dermatology, Wake Forest School of Medicine, WinstonSalem, North Carolina.
Corresponding Author: Hossein Alinia, MD, Center for Dermatology Research, Department of Dermatology, Wake Forest School of Medicine, 4618 Country Club Rd, Winston-Salem, NC 27104 (haliniamd @gmail.com). jamadermatology.com
Assessing Medication Adherence Using Indirect Self-report Poor adherence to medication is common, particularly in patients with chronic diseases who are prescribed multiple medications. A major public health problem, nonadherence is associated with poor clinical outcomes, increased health care costs, prolonged hospitalization, and higher mortality and morbidity. Assessing patients’ medication adherence may be helpful for assessing responses to treatment and for modifying treatment regimens.1,2 Many measurement tools have been suggested, and these methods can be divided into biochemical and pharmacologic markers of drug levels vs methods that quantify how many pills were taken. These latter methods include objective methods (eg, medical records and administration databases, pill count, and electronic monitoring systems) and subjective methods (eg, selfreport questionnaires). Each of these methods has its own strengths and limitations, and none of them covers all aspects of the complex and multidimensional nonadherence problem.1,3 While objective measures provide more reliable assessments of adherence, they are costly and not practical for use in routine clinical settings. Self-report of adherence is the most practical instrument for clinical use but is of limited accuracy.1,3,4 The correlation between medication adherence reported by selfreport questionnaires and electronic monitoring systems varies from 0.24 to 0.87 in different studies and reflects the fact that patients tend to overestimate their adherence in self-reports.2 Self-reported adherence is confounded by many biases, leading to overestimation of adherence.2,3,5 Patients are particularly prone to recall error when the time interval between drug consumption and assessment increases; they tend to recall the routine or intention to take medication instead of actual behavior.1,3 Self-report questionnaires generally focus on undesirable aspects of nonadherence that might make patients feel defensive. If patients think their report of poor adherence will cause an unpleasant effect, it may cause them to inaccurately self-report.3 In theory, using lessjudgmental direct questions about adherence may be useful,3 but one study found that less-judgmental direct questioning did not significantly improve the accuracy of patients’ self-report.4,5 When the subject of a question might make the respondents uncomfortable, using indirect questioning, with less threatening words and options, may lead to more accurate responses. Moreover, developing indirect questions that focus on patients’ current situation instead of relying on their long-term memory may further enhance accurate reporting. We developed a series of questions based on the process of medication use
that does not rely on the memory of an individual dose to elicit information from patients about adherence without sounding judgmental (Box). Poor adherence to treatment has been underrecognized and should be considered when evaluating poor response to treatment. Using indirect questioning about
Box. Indirect Questions That May Shed Light on Whether Patients Are Nonadherent to Treatment 1. Do you need a refill? a. Yes b. No c. Not applicable 2. When you need a refill, a. I call the pharmacy b. I go by the pharmacy c. I use an online or other electronic refill system d. Not applicable 3. If it is time for a refill and you still have extra medicine, a. I wait to fill the refill b. I fill the refill anyway c. I throw the old medicine away and get the refill d. Not applicable 4. Does the pharmacy send you medication even when you don’t need it? a. Yes b. No c. Not applicable 5. Where do you keep extra (prescribed) medicine that has accumulated? a. In the medicine cabinet b. In the kitchen c. In another room or location d. I dispose of extra medicine e. Not applicable 6. I do the following with extra medicine I’ve accumulated (circle all that apply) a. Return it to the pharmacy b. Donate it to charitable organizations c. Share it with friends and relatives d. Dispose of it e. Not applicable 7. I usually dispose of unused medicine a. Down the sink b. Down the toilet c. In the trash can d. Not applicable 8. Do you keep extra syringes refrigerated? a. Yes b. No c. Not applicable 9. Is the cabinet where you keep extra syringes locked? a. Yes b. No c. Not applicable
JAMA Dermatology August 2014 Volume 150, Number 8
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archderm.jamanetwork.com/ by a Penn State Milton S Hershey Med Ctr User on 05/25/2015
813
Opinion Viewpoint
medication use may provide helpful information about nonadherence as a cause of treatment failure. Additional studies are needed ARTICLE INFORMATION Published Online: June 4, 2014. doi:10.1001/jamadermatol.2014.774. Conflict of Interest Disclosures: Dr Feldman reports being a consultant and speaker for Abbott Laboratories, Amgen, Biogen Idec, Bristol-Myers Squibb, Galderma Laboratories LP, Genentech, GlaxoSmithKline, Janssen, Photomedex, Stiefel, and Warner Chilcott; receiving grants from 3M, Abbott Laboratories, Amgen, Astellas, Aventis Pharmaceuticals, Biogen Idec, Bristol-Myers Squibb, Coria Laboratories, Galderma Laboratories LP, Genentech, GlaxoSmithKline, Janssen, Novartis, Ortho Pharmaceuticals, Pharmaderm, Photomedex, Roche Dermatology, Stiefel, and Warner Chilcott; and receiving stock options from Photomedex. No other disclosures were reported.
to assess the efficacy of using such questions and whether they promote greater capture of nonadherence behaviors.
Funding/Support: The Center for Dermatology Research was supported in part by an unrestricted educational grant from Galderma Laboratories LP.
measured by MEMS and self-reported questionnaires: a meta-analysis. Health Qual Life Outcomes. 2010;8:99. doi:10.1186/1477-7525-8-99.
Role of the Sponsor: The funding source had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
3. Williams AB, Amico KR, Bova C, Womack JA. A proposal for quality standards for measuring medication adherence in research. AIDS Behav. 2013;17(1):284-297.
REFERENCES 1. Lehmann A, Aslani P, Ahmed R, et al. Assessing medication adherence: options to consider. Int J Clin Pharm. 2014;36(1):55-69. 2. Shi L, Liu J, Fonseca V, Walker P, Kalsekar A, Pawaskar M. Correlation between adherence rates
4. Garfield S, Clifford S, Eliasson L, Barber N, Willson A. Suitability of measures of self-reported medication adherence for routine clinical use: a systematic review. BMC Med Res Methodol. 2011; 11:149. doi:10.1186/1471-2288-11-149. 5. Wagner G, Miller LG. Is the influence of social desirability on patients’ self-reported adherence overrated? J Acquir Immune Defic Syndr. 2004;35 (2):203-204.
NOTABLE NOTES
Demystifying Merkel Robert Denison Griffith, MD; Mohammad-Ali Yazdani Abyaneh, BS; Leyre Falto-Aizpurua, MD; Keyvan Nouri, MD
The Merkel cell represents 1 of the 4 types of cells that make up the epidermis. But how did it get its name? Friedrich Sigmund Merkel was born in Nuremberg, Germany, in 1845. He earned his medical degree from the University of Erlangen at 24 years of age. After medical school, he accepted a position of prosector at the University Medical Center of Göttingen. As prosector, Merkel was afforded the opportunity to work under Jacob Henle, who was the director of anatomy and the person for which the loop of Henle is named. During this time, Merkel began dating the daughter of his mentor—Anne Henle—who later became his wife. Merkel left Göttingen in 1872 to join the staff at the University of Rostock.1 While working as a professor of anatomy and histopathology at Rostock in 1875, Merkel first described large, pale cells within the epidermis that were intimate with nerve terminals. He referred to the cell that would later come to bear his name as Tastzellen, which translates to “tactile cells.” Moreover, he also referred to groups of these cells in close association with the terminal bulbs of myelinated afferent neurons as Tastkörperchen, which translates to “tactile corpuscles.” These descriptions demonstrate Merkel’s insight that these cells functioned as mechanoreceptors of the skin.2 The eponym Merkel cell, however, was not used until 1878, when Robert Bonnet first used the term when referring to the cells that Merkel had described 3 years prior. Merkel also made a number of contributions to the field of medicine outside of his description of the Merkel cell. Notably, he is credited with
814
the introduction of xylene for use as a clearing agent in the histologic staining process. Merkel is also known for his multivolume textbook on human anatomy and is credited as the first person to produce anatomical illustrations with the color scheme that is used by most anatomy texts today: red for arteries, blue for veins, and yellow for nerves.3 Ninety-five years after Dr Merkel’s death in 1919, xylene is still the most commonly used clearing agent in the histologic staining process; many gross anatomy texts still use his color scheme for labeling arteries, veins, and nerves; and the Merkel cell is mentioned in just about all dermatology and dermatopathology texts today. Author Affiliations: Department of Dermatology and Cutaneous Surgery, Miller School of Medicine, University of Miami, Miami, Florida. Corresponding Author: Robert Denison Griffith, MD, Department of Dermatology and Cutaneous Surgery, Miller School of Medicine, University of Miami, 1475 NW 12th Ave, Second Floor, Miami, FL 33136 ([email protected] .edu). 1. Weissmann A, Camisa C. Friedrich Sigmund Merkel, part I: the man. Am J Dermatopathol. 1982;4(6):521-526. 2. Halata Z, Grim M, Bauman KI. Friedrich Sigmund Merkel and his “Merkel cell”: morphology, development, and physiology: review and new results. Anat Rec A Discov Mol Cell Evol Biol. 2003;271(1):225-239. 3. Merkel cell. http://www.merriam-webster.com/medical/merkel%20cell. Accessed January 29, 2014.
JAMA Dermatology August 2014 Volume 150, Number 8
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archderm.jamanetwork.com/ by a Penn State Milton S Hershey Med Ctr User on 05/25/2015
jamadermatology.com
VIEWPOINT
Hossein Alinia, MD Center for Dermatology Research, Department of Dermatology, Wake Forest School of Medicine, WinstonSalem, North Carolina. Steven R. Feldman, MD, PhD Center for Dermatology Research, Department of Dermatology, Wake Forest School of Medicine, WinstonSalem, North Carolina.
Corresponding Author: Hossein Alinia, MD, Center for Dermatology Research, Department of Dermatology, Wake Forest School of Medicine, 4618 Country Club Rd, Winston-Salem, NC 27104 (haliniamd @gmail.com). jamadermatology.com
Assessing Medication Adherence Using Indirect Self-report Poor adherence to medication is common, particularly in patients with chronic diseases who are prescribed multiple medications. A major public health problem, nonadherence is associated with poor clinical outcomes, increased health care costs, prolonged hospitalization, and higher mortality and morbidity. Assessing patients’ medication adherence may be helpful for assessing responses to treatment and for modifying treatment regimens.1,2 Many measurement tools have been suggested, and these methods can be divided into biochemical and pharmacologic markers of drug levels vs methods that quantify how many pills were taken. These latter methods include objective methods (eg, medical records and administration databases, pill count, and electronic monitoring systems) and subjective methods (eg, selfreport questionnaires). Each of these methods has its own strengths and limitations, and none of them covers all aspects of the complex and multidimensional nonadherence problem.1,3 While objective measures provide more reliable assessments of adherence, they are costly and not practical for use in routine clinical settings. Self-report of adherence is the most practical instrument for clinical use but is of limited accuracy.1,3,4 The correlation between medication adherence reported by selfreport questionnaires and electronic monitoring systems varies from 0.24 to 0.87 in different studies and reflects the fact that patients tend to overestimate their adherence in self-reports.2 Self-reported adherence is confounded by many biases, leading to overestimation of adherence.2,3,5 Patients are particularly prone to recall error when the time interval between drug consumption and assessment increases; they tend to recall the routine or intention to take medication instead of actual behavior.1,3 Self-report questionnaires generally focus on undesirable aspects of nonadherence that might make patients feel defensive. If patients think their report of poor adherence will cause an unpleasant effect, it may cause them to inaccurately self-report.3 In theory, using lessjudgmental direct questions about adherence may be useful,3 but one study found that less-judgmental direct questioning did not significantly improve the accuracy of patients’ self-report.4,5 When the subject of a question might make the respondents uncomfortable, using indirect questioning, with less threatening words and options, may lead to more accurate responses. Moreover, developing indirect questions that focus on patients’ current situation instead of relying on their long-term memory may further enhance accurate reporting. We developed a series of questions based on the process of medication use
that does not rely on the memory of an individual dose to elicit information from patients about adherence without sounding judgmental (Box). Poor adherence to treatment has been underrecognized and should be considered when evaluating poor response to treatment. Using indirect questioning about
Box. Indirect Questions That May Shed Light on Whether Patients Are Nonadherent to Treatment 1. Do you need a refill? a. Yes b. No c. Not applicable 2. When you need a refill, a. I call the pharmacy b. I go by the pharmacy c. I use an online or other electronic refill system d. Not applicable 3. If it is time for a refill and you still have extra medicine, a. I wait to fill the refill b. I fill the refill anyway c. I throw the old medicine away and get the refill d. Not applicable 4. Does the pharmacy send you medication even when you don’t need it? a. Yes b. No c. Not applicable 5. Where do you keep extra (prescribed) medicine that has accumulated? a. In the medicine cabinet b. In the kitchen c. In another room or location d. I dispose of extra medicine e. Not applicable 6. I do the following with extra medicine I’ve accumulated (circle all that apply) a. Return it to the pharmacy b. Donate it to charitable organizations c. Share it with friends and relatives d. Dispose of it e. Not applicable 7. I usually dispose of unused medicine a. Down the sink b. Down the toilet c. In the trash can d. Not applicable 8. Do you keep extra syringes refrigerated? a. Yes b. No c. Not applicable 9. Is the cabinet where you keep extra syringes locked? a. Yes b. No c. Not applicable
JAMA Dermatology August 2014 Volume 150, Number 8
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archderm.jamanetwork.com/ by a Penn State Milton S Hershey Med Ctr User on 05/25/2015
813
Opinion Viewpoint
medication use may provide helpful information about nonadherence as a cause of treatment failure. Additional studies are needed ARTICLE INFORMATION Published Online: June 4, 2014. doi:10.1001/jamadermatol.2014.774. Conflict of Interest Disclosures: Dr Feldman reports being a consultant and speaker for Abbott Laboratories, Amgen, Biogen Idec, Bristol-Myers Squibb, Galderma Laboratories LP, Genentech, GlaxoSmithKline, Janssen, Photomedex, Stiefel, and Warner Chilcott; receiving grants from 3M, Abbott Laboratories, Amgen, Astellas, Aventis Pharmaceuticals, Biogen Idec, Bristol-Myers Squibb, Coria Laboratories, Galderma Laboratories LP, Genentech, GlaxoSmithKline, Janssen, Novartis, Ortho Pharmaceuticals, Pharmaderm, Photomedex, Roche Dermatology, Stiefel, and Warner Chilcott; and receiving stock options from Photomedex. No other disclosures were reported.
to assess the efficacy of using such questions and whether they promote greater capture of nonadherence behaviors.
Funding/Support: The Center for Dermatology Research was supported in part by an unrestricted educational grant from Galderma Laboratories LP.
measured by MEMS and self-reported questionnaires: a meta-analysis. Health Qual Life Outcomes. 2010;8:99. doi:10.1186/1477-7525-8-99.
Role of the Sponsor: The funding source had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
3. Williams AB, Amico KR, Bova C, Womack JA. A proposal for quality standards for measuring medication adherence in research. AIDS Behav. 2013;17(1):284-297.
REFERENCES 1. Lehmann A, Aslani P, Ahmed R, et al. Assessing medication adherence: options to consider. Int J Clin Pharm. 2014;36(1):55-69. 2. Shi L, Liu J, Fonseca V, Walker P, Kalsekar A, Pawaskar M. Correlation between adherence rates
4. Garfield S, Clifford S, Eliasson L, Barber N, Willson A. Suitability of measures of self-reported medication adherence for routine clinical use: a systematic review. BMC Med Res Methodol. 2011; 11:149. doi:10.1186/1471-2288-11-149. 5. Wagner G, Miller LG. Is the influence of social desirability on patients’ self-reported adherence overrated? J Acquir Immune Defic Syndr. 2004;35 (2):203-204.
NOTABLE NOTES
Demystifying Merkel Robert Denison Griffith, MD; Mohammad-Ali Yazdani Abyaneh, BS; Leyre Falto-Aizpurua, MD; Keyvan Nouri, MD
The Merkel cell represents 1 of the 4 types of cells that make up the epidermis. But how did it get its name? Friedrich Sigmund Merkel was born in Nuremberg, Germany, in 1845. He earned his medical degree from the University of Erlangen at 24 years of age. After medical school, he accepted a position of prosector at the University Medical Center of Göttingen. As prosector, Merkel was afforded the opportunity to work under Jacob Henle, who was the director of anatomy and the person for which the loop of Henle is named. During this time, Merkel began dating the daughter of his mentor—Anne Henle—who later became his wife. Merkel left Göttingen in 1872 to join the staff at the University of Rostock.1 While working as a professor of anatomy and histopathology at Rostock in 1875, Merkel first described large, pale cells within the epidermis that were intimate with nerve terminals. He referred to the cell that would later come to bear his name as Tastzellen, which translates to “tactile cells.” Moreover, he also referred to groups of these cells in close association with the terminal bulbs of myelinated afferent neurons as Tastkörperchen, which translates to “tactile corpuscles.” These descriptions demonstrate Merkel’s insight that these cells functioned as mechanoreceptors of the skin.2 The eponym Merkel cell, however, was not used until 1878, when Robert Bonnet first used the term when referring to the cells that Merkel had described 3 years prior. Merkel also made a number of contributions to the field of medicine outside of his description of the Merkel cell. Notably, he is credited with
814
the introduction of xylene for use as a clearing agent in the histologic staining process. Merkel is also known for his multivolume textbook on human anatomy and is credited as the first person to produce anatomical illustrations with the color scheme that is used by most anatomy texts today: red for arteries, blue for veins, and yellow for nerves.3 Ninety-five years after Dr Merkel’s death in 1919, xylene is still the most commonly used clearing agent in the histologic staining process; many gross anatomy texts still use his color scheme for labeling arteries, veins, and nerves; and the Merkel cell is mentioned in just about all dermatology and dermatopathology texts today. Author Affiliations: Department of Dermatology and Cutaneous Surgery, Miller School of Medicine, University of Miami, Miami, Florida. Corresponding Author: Robert Denison Griffith, MD, Department of Dermatology and Cutaneous Surgery, Miller School of Medicine, University of Miami, 1475 NW 12th Ave, Second Floor, Miami, FL 33136 ([email protected] .edu). 1. Weissmann A, Camisa C. Friedrich Sigmund Merkel, part I: the man. Am J Dermatopathol. 1982;4(6):521-526. 2. Halata Z, Grim M, Bauman KI. Friedrich Sigmund Merkel and his “Merkel cell”: morphology, development, and physiology: review and new results. Anat Rec A Discov Mol Cell Evol Biol. 2003;271(1):225-239. 3. Merkel cell. http://www.merriam-webster.com/medical/merkel%20cell. Accessed January 29, 2014.
JAMA Dermatology August 2014 Volume 150, Number 8
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archderm.jamanetwork.com/ by a Penn State Milton S Hershey Med Ctr User on 05/25/2015
jamadermatology.com
